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Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 451 records · Page 25Linked to original sources

The blockade of Fc receptor-mediated clearance of immune complexes in vivo by a monoclonal antibody (2.4G2) directed against Fc receptors on murine leukocytes.

To evaluate the feasibility of using a monoclonal anti-Fc receptor antibody to alter Fc receptor function in vivo, the disappearance of radiolabeled human serum albumin-rabbit anti-human serum albumin (HSA-anti-HSA) complexes was studied in mice before and after the infusion of 2.4G2, a monoclonal antibody (developed by J. Unkeless). 2.4G2 specifically binds to Fc receptors on mouse macrophages. Under standardized conditions, 6.1% of an i.v. administered dose of anti-HSA was sequestered in the liver of B6/D2J mice. When HSA-anti-HSA complexes were administered, 53.4% were sequestered. If 8 micrograms/g body weight of 2.4G2 was infused i.p. 1.5 hr before HSA-anti-HSA, only 13.7% of the infused complexes were sequestered in the liver. The inhibition in Fc receptor-mediated sequestration produced by this dose of antibody persisted for at least 24 hr. A dose of 1 to 2 micrograms/g was sufficient to inhibit sequestration by 50%. Animals receiving daily injections of 2.4G2 cleared immune complexes from their blood much more slowly than untreated animals. Because 2.4G2 was not cytotoxic to peritoneal macrophages in vitro in the presence of serum, and because comparable inhibition of Fc receptor function was observed in vivo in C5-deficient mice, blockade of function does not depend upon complement-mediated lysis of macrophages. The maximal degree of inhibition of Fc receptor function obtained by using intact 2.4G2 was about twice that observed by using Fab fragments of 2.4G2 to block receptors. In addition to its effect on Fc receptor function, 2.4G2 also had a small but significant inhibitory effect upon the clearance of 125I-labeled heat-aggregated HSA by the mononuclear phagocyte system both in intact and C5-deficient mice. We conclude that 2.4G2 is a potent inhibitor of IgG Fc receptor-mediated immune clearance in vivo.

Animals↗

Differences in anorectal manometry between patients with haemorrhoids and patients with descending perineum syndrome: implications for management.

Anorectal manometry was carried out at rest, during balloon distension of the rectum and during rectal infusion of saline in 19 patients with haemorrhoids, 30 patients with descending perineum syndrome and 21 controls. Basal and squeeze pressures were significantly higher in patients with haemorrhoids than patients with the descending perineum syndrome. A lower rectal volume was required to inhibit internal sphincter tone in patients with descending perineum syndrome compared with control subjects or patients with haemorrhoids. During rectal infusion of saline basal and peak anal pressures in patients with the descending perineum syndrome were lower than in haemorrhoid patients. Peak rectal pressure was abnormally high in both groups. These differences in anorectal function suggest that despite a similar presentation, the two conditions have a different pathogenesis. Moreover, inappropriate anal sphincter stretch or mucosal excision in patients with descending perineum syndrome may lead to severe incontinence.

Anal Canal↗

Quantitation of cutaneous toxicity: an in vitro approach using skin organ culture.

A short-term (48 hr) organ culture system for maintaining metabolically viable and structurally intact mouse skin has been developed. With the culture system, the responses of skin to in vitro physical and chemical insults were assessed by histologic examination and selected biochemical measurements in an attempt to establish a quantitative basis for the evaluation of cutaneous toxicity in vitro. In studies with mouse skin in organ culture following either freeze-thaw treatment (physical insult) or a single in vitro topical application of tributyltin chloride (10 to 1000 nmole/cm2), deleterious morphologic changes were observed. The degree of cellular injury was reflected by inhibition of in vitro incorporation of [3H]thymidine and [14C]leucine into epidermal DNA and protein, respectively; there also was leakage of intracellular enzymes into the culture medium in a dose and time related manner. These biochemical parameters are sensitive indicators of cellular injury; as such they may offer a simple, sensitive, and quantitative measure for assessing cutaneous toxicity of chemicals in vitro.

Animals↗

Percutaneous initiation of cardiopulmonary bypass.

Improved technology has allowed us to develop support pumps that can be applied rapidly and safely. A system utilizing thin-walled (4 mm inner diameter) percutaneously inserted sheaths has been designed for rapid bedside arterial and central venous cannulation to establish femoral arterial and venous cardiopulmonary bypass. The system utilizes two 30-cm-long large-bore, thin-walled (end and side holes) venous cannulas and a single 15-cm-long (end hole) arterial reperfusion cannula, which is connected to a pediatric oxygenator and a vortex pump head. Five patients with refractory cardiac arrest who could not be resuscitated by conventional means were revived with this system. Application time was approximately five minutes. This system appears to be an easily applied and reliable short-term mechanical support device.

Cardiopulmonary Bypass↗

Organization and function of a regional pediatric trauma center: does a system of management improve outcome?

Since 1975, more than one thousand children with life-threatening injuries have been preferentially transported to our statewide Regional Pediatric Trauma Center by helicopter or city ambulance. Initial care is provided by emergency medical technicians with special instruction in the handling of pediatric trauma. More than half the children admitted to our service were injured in motor vehicle/pedestrian or motor vehicle/bicycle accidents. Have care and outcome improved? This system provides for excellent first aid at the scene and more rapid radio-directed transport to the trauma center where in-hospital management is provided by pediatric and surgical personnel experienced in the treatment of all aspects of childhood trauma. We have organized weekly trauma morbidity and mortality rounds and have established a trauma registry and index of severity. Pelvic fractures from blunt trauma had a mortality in this series of 1.4%, the lowest of any reported experience. Between January 1976 and December 1979, 46 children with coma of longer than 24 hours' duration were treated in the Pediatric Intensive Care Unit. The mortality rate was still high (38%) but employing intracranial monitoring and aggressive control of brain edema, 88% of the survivors had a good recovery without major motor or intellectual defects. The large volume of cases allows for development and evaluation of new techniques in trauma management and invaluable experience in the training of general surgical residents, pediatricians, and emergency physicians.

Adolescent↗

Effects of age, gender, and cigarette smoking on human immunoregulatory T-cell subsets: establishment of normal ranges and comparison with patients with colorectal cancer and multiple sclerosis.

Normal ranges for peripheral circulating mature functional T cells (OKT3+), T helper-inducer cells (OKT4+), and T cytotoxic-suppressor cells (OKT8+) were determined in 161 normal male and female volunteers. Children between 5 and 15 years of age showed higher circulating OKT3+ cell numbers than adults, and in male children the circulating OKT4+ cell number was also higher. In adults, females demonstrated higher circulating OKT4+ cell numbers than males, and smokers demonstrated higher circulating numbers of both OKT3+ and OKT4+ cells than nonsmokers. There was a significant interaction between gender and smoking, with female smokers exhibiting the highest circulating OKT3+ cell numbers. Two groups of patients entering longitudinal T-cell subset monitoring studies were compared to their appropriate normal control groups. It was found that 48% of patients with colorectal cancer were T-cell (OKT3+) lymphopenic at presentation, and that 62% had a low OKT4/OKT8 ratio. Colorectal surgery tended to correct this T-cell lymphopenia. However, only transient rises in low OKT4/OKT8 ratios were observed after surgery. Of 11 patients with multiple sclerosis in a trial of transfer factor therapy, 7 were found to have high OKT4/OKT8 ratios prior to treatment; these ratios have persisted to date during treatment.

Adolescent↗

Use of anorectal manometry during rectal infusion of saline to investigate sphincter function in incontinent patients.

Anal and rectal pressures and external sphincter electromyogram were recorded continuously during rectal infusion of 1.5 L saline in 18 normal subjects and 37 patients who complained of diarrhea and fecal incontinence. All subjects exhibited a pattern of regular fluctuations in anorectal pressure and electromyogram. All except 1 of the normal subjects were able to retain 1500 ml saline without leakage, and their pressure record comprised simultaneous rectal contractions, internal sphincter relaxations, and external sphincter contractions. None of the incontinent patients were able to retain 1500 ml saline without leakages, and leakages always coincided with the peaks of rectal pressure. Two manometric patterns were observed. Fifty-nine percent of incontinent patients exhibited a pattern of contractions of similar profile occurring throughout the anorectum. This finding was associated with low basal sphincter pressures, an easily inhibited anal sphincter tone, an obtuse anorectal angle, and a funnel-shaped configuration to the anal canal. These results suggested that, in this group, the internal sphincter was weak and easily inhibited so that the whole anorectum behaved as one fluid-filled compartment recording contractions of the external sphincter. The remaining 41% of incontinent patients exhibited a normal pattern of anorectal pressure fluctuations and had normal maximum basal pressures, although maximum squeeze pressures, rectoanal inhibitory reflex, and anorectal angles were abnormal. Peak rectal pressures were abnormally high in this group during saline infusion, suggesting that abnormally strong rectal contractions may play a role in the incontinence in this group.

Adult↗

Effects of conjunctival resection on the corneal immune response.

In order to evaluate the effect of perilimbal conjunctival resection on the corneal immune response, we immunized rabbits with either intravenous or topical administration of bovine gamma globulin. After unilateral perilimbal conjunctival resection, the corneas were challenged with intracorneal injections of bovine gamma globulin. Perilimbal conjunctival resection prevented the development of peripheral corneal infiltrates in the rabbits immunized intravenously (P less than .0016) but not in those immunized topically. All the animals developed antibody titers to bovine gamma globulin. Similarly, perilimbal conjunctival resection did not prevent corneal graft rejection in rabbits sensitized to their donors by previous skin grafting.

Administration, Topical↗

Retinofugal pathways from albino eyes embryonically transplanted to normal and albino axolotls.

Albino axolotl eyes were transplanted embryonically to normal and albino axolotl hosts. The animals were allowed to mature for several months and then their transplanted eyes were injected with tritiated proline. The projections from these albino eyes were compared with those obtained from similar transplants of normally pigmented eyes. Special attention was paid to the crossed and uncrossed components of the projections. No differences were found between normal and albino transplants. These results indicate that abnormal retinofugal crossing, which results from a lack of pigmentation in the mammalian eye, does not occur in the axolotl even when the fraction of retinal cells projecting ipsilaterally is experimentally increased by transplanting supernumerary eyes into embryos.

Afferent Pathways↗

Alamethicin channels incorporated into frog node of ranvier: calcium-induced inactivation and membrane surface charges.

Alamethicin, a peptide antibiotic, partitions into artificial lipid bilayer membranes and into frog myelinated nerve membranes, inducing a voltage-dependent conductance. Discrete changes in conductance representing single-channel events with multiple open states can be detected in either frog node or lipid bilayer membranes. In 120 mM salt solution, the average conductance of a single channel is approximately 600 pS. The channel lifetimes are roughly two times longer in the node membrane than in a phosphatidylethanolamine bilayer at the same membrane potential. With 2 or 20 mM external Ca and internal CsCl, the alamethicin-induced conductance of frog nodal membrane inactivates. Inactivation is abolished by internal EGTA, suggesting that internal accumulation of calcium ions is responsible for the inactivation, through binding of Ca to negative internal surface charges. As a probe for both external and internal surface charges, alamethicin indicates a surface potential difference of approximately -20 to -30 mV, with the inner surface more negative. This surface charge asymmetry is opposite to the surface potential distribution near sodium channels.

Alamethicin↗

Muscle strength and balance in post-stroke patients.

Isokinetic torque of the knee and elbow during maximal extension and flexion and isometric strength of the handgrip, as well as balance and some circulatory variables, were tested in 37 patients one year after an acute stroke. Correlations with locomotion, household work and other activities of daily living (ADL) were tested. Male patients who had received special activation on the ward for up to 4 weeks after the stroke showed a significantly smaller difference in strength between the paretic and non-paretic knee at an angular velocity of 90 degrees per second than males who had received only routine activation on their ward. There was a high correlation between locomotion and the isokinetic torque of the paretic knee and also between locomotion and balance. The correlations between elbow strength and ADL functions were weaker. It was concluded that the evaluation of the isokinetic muscle torque of the knee and the balance tests are valid instruments for estimating functional capacity after a stroke.

Activities of Daily Living↗